Usage
Procarbazine is an antineoplastic agent, specifically an alkylating agent, primarily used in combination chemotherapy regimens for the treatment of stage III and IV Hodgkin lymphoma (Hodgkin’s disease). It is often part of the BEACOPP, COPP, and MOPP regimens. While it has shown some activity against other malignancies like brain tumors, its use in these conditions is limited.
Alternate Names
- International Nonproprietary Name (INN): Procarbazine
- Chemical name: N-isopropyl-α-(2-methylhydrazino)-p-toluamide monohydrochloride
- Brand name: Matulane
How It Works
Pharmacodynamics: Procarbazine exerts its cytotoxic effects through multiple mechanisms, primarily alkylation of DNA and RNA. This leads to DNA strand breaks, inhibiting DNA and RNA synthesis, ultimately causing cell death. It also has some monoamine oxidase inhibitor (MAOI) activity.
Pharmacokinetics: Procarbazine is well-absorbed orally. It undergoes extensive metabolism in the liver, including by CYP450 enzymes, to several active metabolites, including azo-procarbazine and isopropylcarbazic acid. Elimination is primarily through renal excretion, with some hepatic elimination.
Mode of Action: Procarbazine acts as an alkylating agent by forming reactive species that covalently bind to DNA and RNA, resulting in DNA strand breaks, which subsequently inhibit nucleic acid synthesis. Its MAOI activity contributes to its side effect profile.
Receptor Binding/Enzyme Inhibition: Procarbazine’s primary mechanism is DNA alkylation. Its MAOI activity inhibits the enzyme monoamine oxidase, which metabolizes neurotransmitters like dopamine, serotonin, and norepinephrine.
Elimination Pathways: Procarbazine and its metabolites are eliminated primarily via the kidneys, with some hepatic excretion.
Dosage
Standard Dosage
Adults:
Children:
- 50 mg/m²/day orally for the first week.
- Increase to 100 mg/m²/day until maximum response or toxicity.
- Maintenance dose: 50 mg/m²/day.
Special Cases:
- Elderly Patients: Use with caution and close monitoring; adjust dose based on renal function.
- Patients with Renal Impairment: Use with caution, adjust dose as necessary based on creatinine clearance.
- Patients with Hepatic Dysfunction: Use with caution, adjust dose as necessary based on liver function tests.
Clinical Use Cases
Procarbazine is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU care, or emergency situations. Its primary use is in the treatment of Hodgkin lymphoma.
Dosage Adjustments
Dose adjustments are based on hematologic toxicity, renal function, hepatic function, and concomitant medications. Close monitoring of blood counts and organ function is crucial during procarbazine therapy.
Side Effects
Common Side Effects
- Nausea and vomiting
- Myelosuppression (leukopenia, thrombocytopenia, anemia)
- Peripheral neuropathy
- Dermatologic reactions (rash, photosensitivity)
Rare but Serious Side Effects
- Pulmonary toxicity
- Secondary malignancies (e.g., leukemia)
- Severe allergic reactions
Long-Term Effects
- Infertility
- Increased risk of secondary malignancies
Adverse Drug Reactions (ADR)
- Severe myelosuppression
- Hepatotoxicity
- Pulmonary toxicity
- Anaphylaxis
Contraindications
- Pre-existing severe bone marrow suppression
- Severe renal or hepatic impairment
- Pregnancy
Drug Interactions
- MAOIs: Concomitant use contraindicated.
- Alcohol: Disulfiram-like reaction.
- CNS depressants: Increased sedation.
- Antihypertensives: Enhanced hypotensive effects.
Pregnancy and Breastfeeding
- Pregnancy Category D: Contraindicated due to teratogenic effects.
- Breastfeeding: Contraindicated.
Drug Profile Summary
- Mechanism of Action: Alkylating agent, DNA and RNA synthesis inhibitor.
- Side Effects: Myelosuppression, nausea/vomiting, peripheral neuropathy.
- Contraindications: Bone marrow suppression, renal/hepatic impairment, pregnancy.
- Drug Interactions: MAOIs, alcohol, CNS depressants.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: CBC, liver function tests, renal function tests.
Popular Combinations
Procarbazine is commonly used as part of the BEACOPP, COPP, and MOPP chemotherapy regimens in the treatment of Hodgkin lymphoma.
Precautions
- Monitor blood counts, liver and kidney function regularly.
- Patient counseling regarding fertility risks.
- Avoid alcohol consumption during treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Procarbazine?
A: See the detailed dosage section above for specific dosages for adults, children, and special populations.
Q2: What is the primary use of Procarbazine?
A: Treatment of stage III and IV Hodgkin lymphoma as part of combination chemotherapy regimens.
Q3: What are the most common side effects?
A: Myelosuppression (low blood counts), nausea, vomiting, and peripheral neuropathy.
Q4: Is Procarbazine safe to use during pregnancy or breastfeeding?
A: No, it’s contraindicated due to risk of fetal harm and excretion into breast milk.
Q5: What are the serious side effects to watch out for?
A: Severe myelosuppression, secondary malignancies, pulmonary toxicity, and severe allergic reactions.
Q6: What are the key drug interactions with Procarbazine?
A: Concomitant use with MAOIs is contraindicated. Interactions can occur with alcohol, CNS depressants, and antihypertensives.
Q7: What are the key monitoring parameters during Procarbazine therapy?
A: Regular monitoring of complete blood counts (CBC), liver function tests, and renal function tests are necessary.
Q8: What precautions should be taken when prescribing Procarbazine?
A: Caution is advised in patients with pre-existing cardiovascular disease, diabetes, or epilepsy. Patients should be counseled on the risk of infertility and avoid alcohol.
Q9: What are the long-term risks associated with Procarbazine use?
A: Increased risk of secondary malignancies, including leukemia, and infertility.
